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Title: Double-walled microspheres for the sustained release of a highly water soluble drug: Characterization and irradiation studies
Authors: Lee, T.H.
Wang, J. 
Wang, C.-H. 
Keywords: Double-walled reservoir microspheres
Poly(D,L-lactic-co-glycolic acid)
Poly(L-lactic acid)
Issue Date: 30-Oct-2002
Citation: Lee, T.H., Wang, J., Wang, C.-H. (2002-10-30). Double-walled microspheres for the sustained release of a highly water soluble drug: Characterization and irradiation studies. Journal of Controlled Release 83 (3) : 437-452. ScholarBank@NUS Repository.
Abstract: Composite double-walled microspheres with biodegradable poly(L-lactic acid) (PLLA) shells and poly(D,L-lactic-co-glycolic acid) (PLGA) cores were fabricated with highly water-soluble etanidazole entrapped within the core as solid crystals. This paper discusses the characterization, in vitro release and the effects of irradiation on this class of microsphere. Through the variation of polymer mass ratios, predictable shell and core dimensions could be fabricated and used to regulate the release rates. A direct and simple method was devised to determine the composition of the shell and core polymer based on the different solubilities of the polymer pair in ethyl acetate. A distribution theory based on solubility parameter explains why highly hydrophilic etanidazole has the tendency to be distributed consistently to the more hydrophilic polymer. Release profiles for normal double-walled samples have about 80% of drug released over 10 days after the initial time lag, while for irradiated double-walled samples, the sustained release lasted for more than 3 weeks. Although sustained release was short of the desired 6-8 weeks required for therapy, a low initial burst of less than 5% and time lags that can be manipulated, allows for administration of these microspheres together with traditional ones to generate pulsatile or new type of releases. The effects of irradiation were also investigated to determine the suitability of these double-walled microspheres as delivery devices to be used in conjunction with radiotherapy. Typical therapeutic dosage of 50 Gy was found to be too mild to have noticeable effects on the polymer and its release profiles, while, sterilization dosages of 25 kGy, lowered the glass transition temperatures and crystalline melting point, indirectly indicating a decrease in molecular weight. This accelerated degradation of the polymer, hence releasing the drug. © 2002 Elsevier Science B.V. All rights reserved.
Source Title: Journal of Controlled Release
ISSN: 01683659
DOI: 10.1016/S0168-3659(02)00235-3
Appears in Collections:Staff Publications

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